title: Preoperative bevacizumab combined with letrozole and chemotherapy in locally advanced ER- and/or PgR-positive breast cancer: clinical and biological activity.
abstract: The antiangiogenic agent bevacizumab showed synergistic effects when combined with chemotherapy in advanced breast cancer. We presently investigated the activity of bevacizumab in combination with chemotherapy, including capecitabine and vinorelbine, and endocrine therapy, including letrozole (+triptorelin in premenopausal women), as primary therapy for patients with ER and/or PgR > or =10% T2-T4a-c, N0-N2, M0 breast cancer. Biological end point included the proliferative activity (Ki67), whereas clinical end points were clinical response rate, pathological complete response (pCR) and tolerability. Circulating endothelial cells (CECs) and their progenitors, as surrogate markers of antiangiogenic activity, were measured at baseline and at surgery.Thirty-six women are evaluable. A clinical response rate of 86% (95% CI, 70-95) and no pCR were observed; Ki67 was significantly decreased by 71% (interquartile range, -82%, -62%). Toxicity was manageable: two grade 3 hypertension, four grade 3 deep venous thrombosis and no grade >2 proteinuria were observed. Treatment significantly decreased the percentage of viable CECs and prevented the chemotherapy-induced mobilisation of circulating progenitors. Basal circulating progenitors were positively associated with clinical response. In conclusion, bevacizumab is feasible and active in association with primary chemoendocrine therapy for ER-positive tumours in terms of proliferation inhibition, clinical response and antiangiogenic activity.
authors.affiliation: Department of Medicine, Research Unit of Medical Senology, European Institute of Oncology Milan, Milan, Italy. rosalba.torrisi@ieo.it
authors.forename: R
authors.initials: R
authors.lastname: Torrisi
authors.forename: V
authors.initials: V
authors.lastname: Bagnardi
authors.forename: A
authors.initials: A
authors.lastname: Cardillo
authors.forename: F
authors.initials: F
authors.lastname: Bertolini
authors.forename: E
authors.initials: E
authors.lastname: Scarano
authors.forename: L
authors.initials: L
authors.lastname: Orlando
authors.forename: P
authors.initials: P
authors.lastname: Mancuso
authors.forename: A
authors.initials: A
authors.lastname: Luini
authors.forename: A
authors.initials: A
authors.lastname: Calleri
authors.forename: G
authors.initials: G
authors.lastname: Viale
authors.forename: A
authors.initials: A
authors.lastname: Goldhirsch
authors.forename: M
authors.initials: M
authors.lastname: Colleoni
mesh_terms: D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage*; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D000068258:Bevacizumab; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D000077289:Letrozole; D008875:Middle Aged; D009367:Neoplasm Staging; D009570:Nitriles / Q000008:administration & dosage*; D011300:Preoperative Care; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D014230:Triazoles / Q000008:administration & dosage*
chemical_list: D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D009570:Nitriles; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D014230:Triazoles; D000068258:Bevacizumab; D000077289:Letrozole